1. Technical Field of the Invention
The present invention relates to measurement of hardness and porosity of an object to be measured (such as a tablet) which is an aggregation of particles.
2. Related Art
Hardness and porosity of a pharmaceutical preparation (tablet and preparation particles forming the tablet) forms important characteristics influencing efficiency of a medicine. In medicines, a solid preparation is manufactured by granulating, tableting, and coating a mixture of raw materials such as drug substance which is an effective component as well as an excipient, a binder, and a disintegrator.
Characteristics of the solid preparation are affected by a crystal form, an average particle diameter, and a granularity distribution of each of raw material. The characteristics of the solid preparation are also affected by conditions of a manufacturing process. The characteristics of the solid preparation are affected by a device scale (capacity), an agitating speed, a pressure, and a temperature for example in a granulation process. The characteristics of the solid preparation are affected by a tableting pressure in a tableting process, for example.
In this way, the characteristics of the solid preparation are affected in a complex way by various factors of the raw materials and the manufacturing process. Therefore, there is a difficulty in a logical estimation of the characteristics of the solid preparation. Thus, the quality of the solid preparation is guaranteed by an empirical design of a batch process and validation.
Meanwhile, according to the guideline of the International Conference on Harmonisation (ICH) of Japan, the United States, and the EU, it is required to sufficiently verify medicine quality risks on the stage of research and development, to acquire a large amount of data by monitoring critical quality attributes (CQAs) associated with the quality risks with high importance in the manufacturing process, and to understand the characteristics based on scientific basis. Then, the Quality by Design (QbD) which determines a design space based on these results and builds the quality in the process is proposed. Therefore, a development of the PAT (Process Analytical Technology) which enables monitoring and analysis of the CQA in real time and a nondestructive manner in the development of the medicine is expected.
The hardness and the porosity of the medical preparation are preparation attributes which can be CQAs. The measurement of the hardness is carried out by calculation of the density (density and hardness correlates with each other) by measurement of the weight and the volume and by a measurement of hardness through a destructive test with a tablet hardness tester. Moreover, the helium pycnometer and the mercury intrusion porosimetry are usually used to measure the porosity. However, both of these methods lack real time property, are destructive measurements, and are thus not suitable for PAT tool.
A nondestructive analysis by means of the near infrared (NIR) method for the tablet hardness and the porosity is proposed (refer to Non-patent Document 1).
It should be noted that Non-patent literature 2 describes how to calculate the complex amplitude transmittance.